Telomerase activity in cells with arsenic-induced genomic instability

It is well known that the occurrence of dicentric chromosomes represent signature of telomere dysfunction and is a clear symptom of genomic instability. V79 Chinese hamster cells, treated with 10μM sodium arsenite for 24h and allowed to grow in drug-free medium (ASO cells), showed genomic instability with aneuploidy and nuclear abnormalities as well as the appearance of dicentric chromosomes since the 90th cell generation. TRAP assay was performed on growing ASO cells and on clones isolated during the course of the expanded growth. As expected, some clones with dicentric chromosomes and severely reduced telomerase activity went to death; surprisingly, other clones also bearing chromosomal end-to-end fusions maintained telomerase activity and were capable of proliferating accumulating genomic instability. These findings indicate that arsenic induces continuing instability by telomere dysfunction and suggest that this abnormal phenotype could arise from deregulation of the protein complex that protect chromosome ends from degradation and end-to-end fusion. Preliminary results by FISH analysis, performed on the unstable clones with active telomerase, seem to be in favour of a possible involvement of DNA damage response proteins. In fact, the most part of the dicentric rearrangements showed telomeric sequences clearly detectable at fusion point, in agreement with some data reported for mice Ku-deficient cells in which genomic instability is related to the impairment of DNA damage repair mechanism.